The long term objectives of the proposed research are to elucidate the roles of parathyroid hormone-related protein (PTH-rP) in the female reproductive tract. It is known that: 1) PTH-rP inhibits uterine contraction, 2) PTH-rP mRNA is expressed in the uterus, and 3) PTH-rP has been localized in the uterus by immunocytochemistry. However, how PTH-rP inhibits uterine contraction and the nature of cells directly responsible for this relaxing action of PTH-rP, are unclear. The first specific aim addresses the hypothesis that PTH-rP inhibition of uterine contraction involves nitric oxide (NO). The proposed experiments will examine if PTH-rP directly enhances the formation of NO. Also, the possible involvement of PTH-rP and intrinsic NADPH-diaphorase- positive nerves (indicative of NO synthetase). To better understand the role of PTH-rP, it would be meaningful to identify the location of receptors for this peptide. The second specific aim addresses the hypothesis that specific receptors for PTH-rP are located in the uterus in areas optimal to modify myometrial activity. The uterus expresses high levels of PTH-rP mRNA during late pregnancy. The third specific aim addresses the hypothesis that specific receptors for PTH-rP are up- regulated during pregnancy. The proposed experiments will examine whether localization and specific binding of PTH-rP are in the myometrium, the connective tissue and/or associated with tissues that are NADPH-diaphorase-positive in non pregnant and pregnant uteri using receptor auto radiography.